Health status of children conceived by assisted reproductive technologies: endocrinologist’s position

Cover Page

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access


Assisted reproductive technologies (ART) are currently widely used around the world because of the increased prevalence of infertility (presently, about 15% of married couples suffer from infertility), as well as the increased access to treatment and public funding for this method. Hence, the number of children conceived by ART is steadily increasing every year.

This review focuses on the pressing problem of the health status of children conceived by assisted reproductive technologies (ART) by analyzing modern publications on the state of physical, gonadal and psychosomatic development, features of the endocrine system and cardiometabolic diseases, the risk of imprinting changes, congenital malformations and oncological disorders.

The data presented that there is no increased risk of childhood cancer or deterioration in quality of life. However, it is expected that the cardiovascular and metabolic risk factors found in childhood can worsen in later life and may ultimately be responsible for chronic cardiometabolic disease. Furthermore, the issue of fertility, especially in the male population conceived by ART, remains open, thus requiring additional longer-term research.

Full Text

Restricted Access

About the authors

Zinaida S. Zyuzikova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0001-6709-8231
SPIN-code: 6731-8990

MD, PhD student

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

Natalya N. Volevodz

Endocrinology Research Centre

Author for correspondence.
ORCID iD: 0000-0001-6470-6318
SPIN-code: 1127-0933

MD, PhD, Professor

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

Olga R. Grigoryan

Endocrinology Research Centre

ORCID iD: 0000-0003-4979-7420
SPIN-code: 3060-8242


Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

Elena I. Degtyareva

National Medical Research Center of Obstetrics, Gynecology and Perinatology

ORCID iD: 0000-0002-8341-4449
SPIN-code: 5641-6913


Russian Federation, 4, akademika Oparina street, Moscow, 117997

Ivan I. Dedov

Endocrinology Research Centre

ORCID iD: 0000-0002-8175-7886
SPIN-code: 5873-2280

MD, PhD, Professor

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036


  1. Wang Ya, Macaldowie A, Hayward I, et al. Assisted reproductive technology in Australia and New Zealand 2009. Canberra: Aihw; 2011.
  2. Sandin S, Nygren KG, Iliadou A, et al. Autism and mental retardation among offspring born after in vitro fertilization. JAMA. 2013;310(1):75-84. doi: 10.1001/Jama.2013.7222
  3. Luke B. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on us population-based studies. Am J Obstet Gynecol. 2017;217(3):270-281. doi: 10.1016/J.Ajog.2017.03.012
  4. European Society of human reproduction and embryology. Art Fact Sheet. Eshre; 2011.
  5. Norman RJ. The power of one and its cost. Med J Aust. 2011; 195(10):564-565. doi: 10.5694/mja11.11283
  6. Корсак В.С., Смирнова А.А., Шурыгина О.В. ВРТ в России. Отчет за 2015 г. В кн.: Российская Ассоциация Репродукции Человека. Регистр ВРТ. Отчет За 2015 г. СПб. 2017. [Korsak VS, Smirnova AA, Shurygina OV. VRT v Rossii. Otchet za 2015. In: Russian association of human reproduction. Registr VRT. Otchet za 2015. Saint-Petersburg 2017. (In Russ.)].
  7. Halliday J. Outcomes of IVF conceptions: are they different? Best Pract Res Clin Obstet Gynaecol. 2007;21(1):67-81. doi: 10.1016/j.bpobgyn.2006.08.004
  8. Hansen M, Bower C, Milne E, et al. Assisted reproductive technologies and the risk of birth defects — a systematic review. Hum Reprod. 2005;20(2):328-338. doi: 10.1093/Humrep/Deh593
  9. Davies MJ, Moore VM, Willson KJ, et al. Reproductive technologies and rhe risk of birth defects. N Engl J Med. 2012;366(19):1803-1813. doi: 10.1056/Nejmoa1008095
  10. Laprise SL. Implications of epigenetics and genomic imprinting in assisted reproductive technologies. Mol Reprod Dev. 2009; 76(11):1006-1018. doi: 10.1002/Mrd.21058
  11. Belva F, Henriet S, Liebaers I, et al. Medical outcome of 8-year-old singleton ICSI children (born >or=32 weeks’ gestation) and a spontaneously conceived comparison group. Hum Reprod. 2007; 22(2):506-515. doi: 10.1093/Humrep/Del372
  12. Strömberg B, Dahlquist G, Ericson A, et al. Neurological sequelaeiIn children born after in vitro fertilisation: a population based study. Lancet. 2002;359(9305):461-465. doi: 10.1016/s0140-6736(02)07674-2
  13. Wang YA, Sullivan EA, Healy DL, Black DA. Perinatal outcomes after assisted reproductive technology treatment in Australia and New Zealand: single versus double embryo transfer. Med J Aust. 2009;190(5):234-237.
  14. Fleming TP, Velazquez MA, Eckert JJ, et al. Nutrition of females during the peri-conceptional period and effects on foetal programming and health of offspring. Anim Reprod Sci. 2012;130(3-4):193-197. doi: 10.1016/j.anireprosci.2012.01.015
  15. Lu YH, Wang N, Jin F. Long-term follow-up of children conceived through assisted reproductive technology. J Zhejiang Univ Sci B. 2013;14(5):359-371. doi: 10.1631/jzus.B1200348
  16. Henningsen AK, Pinborg A, Lidegaard O, et al. Perinatal outcome of singleton siblings born after assisted reproductive technology and spontaneous conception: Danish national sibling-cohort study. Fertil Steril. 2011;95(3):959-963. doi: 10.1016/j.fertnstert.2010.07.1075
  17. Koivurova S, Hartikainen AL, Gissler M, et al. Post-neonatal hospitalization and health care costs among IVF children: a 7-year follow-up study. Hum Reprod. 2007;22(8):2136-2141. doi: 10.1093/humrep/dem150
  18. Kai CM, Main KM, Andersen AN, et al. Serum insulin-like growth factor-I (IGF-I) and growth in children born after assisted reproduction. J Clin Endocrinol Metab. 2006;91(11):4352-4360. doi: 10.1210/Jc.2006-0701
  19. Bonduelle M, Wennerholm UB, Loft A, et al. A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod. 2005;20(2):413-419. doi: 10.1093/humrep/deh592
  20. Ceelen M, Van Weissenbruch MM, Prein J, et al. Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8—18 years of IVF children and spontaneously conceived controls born to subfertile parents. Hum Reprod. 2009;24(11):2788-2795. doi: 10.1093/humrep/dep273
  21. Miles HL, Hofman PL, Peek J, et al. In vitro fertilization improves childhood growth and metabolism. J Clin Endocrinol Metab. 2007;92(9):3441-3445. doi: 10.1210/Jc.2006-2465
  22. Green MP, Mouat F, Miles HL, et al. Anthropometric and endocrine differences exist between children conceived after the transfer of a fresh or thawed embryo compared to naturally conceived controls. Aust N Z J Obstet Gynaecol. 2010;50:25.
  23. Basatemur E, Shevlin M, Sutcliffe A. Growth of children conceived by IVF and ICSI up to 12 years of age. Reprod Biomed Online. 2010;20(1):144-149. doi: 10.1016/j.rbmo.2009.10.006
  24. Ludwig AK, Katalinic A, Thyen U, et al. Physical health at 5.5 years of age of term-born singletons after intracytoplasmic sperm injection: results of a prospective, controlled, single-blinded study. Fertil Steril. 2009;91(1):115-124. doi: 10.1016/J.Fertnstert.2007.11.037
  25. Mau Kai C, Main KM, Andersen AN, et al. Reduced serum testosterone levels in infant boys conceived by intracytoplasmic sperm injection. J Clin Endocrinol Metab. 2007;92(7):2598-2603. doi: 10.1210/jc.2007-0095
  26. De Schepper J, Belva F, Schiettecatte J, et al. Testicular growth and tubular function in prepubertal boys conceived by intracytoplasmic sperm injection. Horm Res. 2009;71(6):359-363. doi: 10.1159/000223421
  27. Belva F, Bonduelle M, Painter RC, et al. Serum inhibin B concentrations in pubertal boys conceived by ICSI: first results. Hum Reprod. 2010;25(11):2811-2814. doi: 10.1093/humrep/deq249
  28. Belva F, Bonduelle M, Schiettecatte J, et al. Salivary testosterone concentrations in pubertal ICSI boys compared with spontaneously conceived boys. Hum Reprod. 2011;26(2):438-441. doi: 10.1093/humrep/deq345
  29. Ceelen M, Van Weissenbruch MM, Vermeiden JP, et al. Pubertal development in children and adolescents born after IVF and spontaneous conception. Hum Reprod. 2008;23(12):2791-2798. doi: 10.1093/humrep/den309
  30. Sakka SD, Loutradis D, Kanaka-Gantenbein C, et al. Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization. Fertil Steril. 2010;94(5):1693-1699. doi: 10.1016/j.fertnstert.2009.09.049
  31. Belva F, Roelants M, Painter R, et al. Pubertal development in ICSI children. Hum Reprod. 2012;27(4):1156-1161. doi: 10.1093/humrep/des001
  32. Beydoun HA, Sicignano N, Beydoun MA, et al. A cross-sectional evaluation of the first cohort of young adults conceived by in vitro fertilization in the United States. Fertil Steril. 2010;94(6):2043-2049. doi: 10.1016/j.fertnstert.2009.12.023
  33. Hart R, Norman RJ. The longer-term health outcomes for children born as a result of IVF treatment: part I — general health outcomes. Hum Reprod Update. 2013;19(3):232-243. doi: 10.1093/humupd/dms062
  34. Sakka SD, Malamitsi-Puchner A, Loutradis D, et al. Euthyroid hyperthyrotropinemia in children born after in vitro fertilization. J Clin Endocrinol Metab. 2009;94(4):1338-1341. doi: 10.1210/jc.2008-1624
  35. Gkourogianni A, Kosteria I, Telonis AG, et al. Plasma metabolomic profiling suggests early indications for predisposition to latent insulin resistance in children conceived by ICSI. Plos One. 2014;9(4):E94001. doi: 10.1371/journal.pone.0094001
  36. Ceelen M, Van Weissenbruch MM, Vermeiden JP, et al. Cardiometabolic differences in children born after in vitro fertilization: follow-up study. J Clin Endocrinol Metab. 2008;93(5):1682-1688. doi: 10.1210/jc.2007-2432
  37. Scherrer U, Rimoldi SF, Rexhaj E, et al. Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies. Circulation. 2012;125(15):1890-1896. doi: 10.1161/circulationaha.111.071183
  38. Ceelen M, Van Weissenbruch MM, Vermeiden JP, et al. Growth and development of children born after in vitro fertilization. Fertil Steril. 2008;90(5):1662-1673. doi: 10.1016/j.fertnstert.2007.09.005
  39. Place I, Englert Y. A prospective longitudinal study of the physical, psychomotor, and intellectual development of singleton children up to 5 years who were conceived by intracytoplasmic sperm injection compared with children conceived spontaneously and by in vitro fertilization. Fertil Steril. 2003;80(6):1388-1397. doi: 10.1016/j.fertnstert.2003.06.004
  40. Koivurova S, Hartikainen AL, Gissler M, et al. Post-neonatal hospitalization and health care costs among IVF children: a 7-year follow-up study. Hum Reprod. 2007;22(8):2136-2141. doi: 10.1093/humrep/dem150 = 17!!!
  41. Group ECW. Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report. J Assist Reprod Genet. 2014;31(8):947-958. doi: 10.1007/s10815-014-0255-7
  42. Wen J, Jiang J, Ding C, et al. Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a metaanalysis. Fertil Steril. 2012;97(6):1331-1337, E1331-E1334. doi: 10.1016/j.fertnstert.2012.02.053
  43. Tararbit K, Houyel L, Bonnet D, et al. Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation. Eur Heart J. 2011;32(4):500-508. doi: 10.1093/eurheartj/ehq440
  44. Rimm AA, Katayama AC, Katayama KP. A Metaanalysis of the Impact of IVF and ICSI on major malformations after adjusting for the effect of subfertility. J Assist Reprod Genet. 2011;28(8):699-705. doi: 10.1007/s10815-011-9583-z
  45. Pontesilli M, Painter Rc, Grooten Ij, et al. Subfertility and assisted reproduction techniques are associated with poorer cardiometabolic profiles in childhood. Reprod Biomed Online. 2015;30(3):258-267. doi: 10.1016/j.rbmo.2014.11.006
  46. Yan J, Huang G, Sun Y, et al. Birth defects after assisted reproductive technologies in China: analysis of 15,405 offspring in seven centers (2004 to 2008). Fertil Steril. 2011;95(1):458-460. doi: 10.1016/j.fertnstert.2010.08.024
  47. Волеводз Н.Н., Зюзикова З.С., Григорян О.Р., Дегтярева Е.И. Вспомогательные репродуктивные технологии: анализ частоты врожденных пороков развития у детей. Международный конгресс «Большие акушерские и неонатальные синдромы — патофизиология и клиническая практика». Санкт-Петербург. 2017 декабрь 14-16. [Volevodz NN, Zyuzikova ZS, Grigoryan OR, Degtyareva EI. Vspomogatel’nye Reproduktivnye Tekhnologii: Analiz chastoty vrozhdennykh porokov razvitiya u detey. In: Proceedings of the Iinternational congress «Large obstetrical and neonatal syndromes — pathophysiology and clinical practice». Saint-Petersberg. 2017 Dec 14-16. (In Russ.)].
  48. Kallen B, Finnstrom O, Nygren KG, Olausson PO. In vitro fertilization in Sweden: hild morbidity including cancer risk. Fertil Steril. 2005;84(3):605-610. doi: 10.1016/j.fertnstert.2005.03.035
  49. Kallen B, Finnstrom O, Lindam A, et al. Cancer risk in children and young adults conceived by in vitro fertilization. Pediatrics. 2010;126(2):270-276. doi: 10.1542/peds.2009-3225
  50. Tomizawa S, Sasaki H. Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell. J Hum Genet. 2012;57(2):84-91. doi: 10.1038/jhg.2011.151
  51. Katari S, Turan N, Bibikova M, et al. DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet. 2009;18(20):3769-3778. doi: 10.1093/hmg/ddp319
  52. Баранов А.А., Намазова-Баранова Л.С., Беляева И.А., и др. Медико-социальные проблемы вспомогательных репродуктивных технологий с позиций педиатрии. // Вестник Российской Академии Медицинских Наук. — 2015. — Т. 70. — № 3. — С. 307—314. [Baranov AA, Namazova-Baranova LS, Belyaeva IA, et al. Medical and social problems of assisted reproductive technologies from the perspective of pediatrics. Annals of the Russian Academy of Medical Sciences. 2015;70(3):307-314. (In Russ.)]. doi: 10.15690/vramn.v70i3.1326
  53. Zhu JL, Hvidtjorn D, Basso O, et al. Parental infertility and cerebral palsy in children. Hum Reprod. 2010;25(12):3142-3145. doi: 10.1093/humrep/deq206
  54. Hvidtjorn D, Schieve L, Schendel D, et al. Cerebral palsy, Autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and metaanalysis. Arch Pediatr Adolesc Med. 2009;163(1):72-83. doi: 10.1001/archpediatrics.2008.507
  55. Кешишян Е.С., Царегородцев А.Д., Зиборова М.И. Состояние здоровья и развития детей, рожденных после экстракорпорального оплодотворения. // Российский Вестник перинатологии и педиатрии. — 2014. — Т. 59. — № 5. — С. 15—25. [Keshishyan ES, Tsaregorodtsev AD, Ziborova MI. The health status of children born after in vitro fertilization. Rossiiskii Vestnik Perinatologii i Pediatrii. 2014;59(5):15-25. (In Russ.)].
  56. Hart R, Norman RJ. The longer-term health outcomes for children born as a result of IVF treatment. Part II — mental health and development outcomes. Hum Reprod Update. 2013;19(3):244-250. doi: 10.1093/humupd/dmt002
  57. Hvidtjorn D, Grove J, Schendel D, et al. Risk of autism spectrum disorders in children born after assisted conception: a population based follow-up study. J Epidemiol Community Health. 2011; 65(6):497-502. doi: 10.1136/jech.2009.093823
  58. Wagenaar K, Van Weissenbruch MM, Knol DL, et al. Behavior and socioemotional functioning in 9—18-year-old children born after in vitro fertilization. Fertil Steril. 2009;92(6):1907-1914. doi: 10.1016/j.fertnstert.2008.09.026
  59. Wagenaar K, Van Weissenbruch MM, Knol DL, et al. Information processing, attention and visual motor function of adolescents born after in vitro fertilization compared with spontaneous conception. Hum Reprod. 2009;24(4):913-921. doi: 10.1093/humrep/den455
  60. Kallen AJ, Finnstrom OO, Lindam AP, et al. Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization? Eur J Paediatr Neurol. 2011;15(3):247-253. doi: 10.1016/j.ejpn.2010.12.004

Supplementary files

There are no supplementary files to display.

Copyright (c) 2021 Zyuzikova Z.S., Volevodz N.N., Grigoryan O.R., Degtyareva E.I., Dedov I.I.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies